Lymphomas are cancerous growths of lymph node cells.
Follicular lymphoma (FL) is a form of lymphoma that is diagnosed in 18,000 Americans and has a worldwide incidence of ˜120,000 cases per year. The clinical behavior of FLs is characterized by slow and relentless growth and inevitable relapse despite intensive chemotherapy.
FLs are considered indolent and slow growing tumors. This is in contradistinction to aggressive lymphomas, where cell cycle lesions/mutations are common and their pathogenic and therapeutic relevance is established (Pasqualucci et al., Nature genetics 43: 830-837 (2011), Morin et al., Nature 476: 298-303 (2011), Schmitz et al., Nature (2012), Monti et al., Cancer Cell 22:359-372 (2012), Lenz et al., Proc Natl Acad Sci USA 105:13520-13525 (2008), Jardin et al., Blood 116:1092-1104 (2010)). Cell cycle lesions have only rarely been reported in FL and their role has remained unclear (Chim et al., Human pathology 38:1849-1857 (2007), Alhejaily et al. Human pathology 42:972-982 (2011), Pruneri et al., International journal of cancer. Journal international du cancer 112:71-77 (2004)).
FLs are genetically defined by the translocation t(14;18) that activates the anti-apoptotic BCL2 (B-cell lymphoma 2) protein. However, BCL2 activation is not sufficient for malignant growth (Staudt, N Engl J Med 356:741-742 (2007)), and therapies that target BCL2 have shown limited efficacy in the treatment of FL.
Effective treatments are needed for this fatal condition.